Romanelli, Maiara Maria
da Costa-Silva, Thais Alves
Dias Ferreira, Daiane
Guerra, Juliana M.
Galisteo, Jr., Andres Jimenez
Pinto, Erika Gracielle
Barbosa, Leandro R. S.
Torres-Santos, Eduardo Caio
Tempone, Andre Gustavo
Total Authors: 10
 Adolfo Lutz Inst, Ctr Parasitol & Mycol, Sao Paulo - Brazil
 Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Lab Bioquim Tripanosomatideos, Pavilhao Leonidas Deane, Rio De Janeiro - Brazil
 Adolfo Lutz Inst, Ctr Pathol, Sao Paulo - Brazil
 Univ Sao Paulo, Hosp Clin HCFMUSP, Fac Med, Sao Paulo - Brazil
 Univ Dundee, Drug Discovery Unit, Life Sci, Dundee - Scotland
 Univ Sao Paulo, Inst Fis, Cidade Univ, Sao Paulo - Brazil
Total Affiliations: 6
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY;
OCT 29 2019.
Web of Science Citations:
Liposomes containing phosphatidylserine (PS) has been used for the delivery of drugs into the intramacrophage milieu. Leishmania (L.) infantum parasites live inside macrophages and cause a fatal and neglected viscerotropic disease, with a toxic treatment. Sertraline was studied as a free formulation (SERT) and also entrapped into phosphatidylserine liposomes (LP-SERT) against intracellular amastigotes and in a murine model of visceral leishmaniasis. LP-SERT showed a potent activity against intracellular amastigotes with an EC50 value of 2.5 mu M. The in vivo efficacy of SERT demonstrated a therapeutic failure. However, when entrapped into negatively charged liposomes (-58 mV) of 125 nm, it significantly reduced the parasite burden in the mice liver by 89% at 1 mg/kg, reducing the serum levels of the cytokine IL-6 and upregulating the levels of the chemokine MCP-1. Histopathological studies demonstrated the presence of an inflammatory infiltrate with the development of granulomas in the liver, suggesting the resolution of the infection in the treated group. Delivery studies showed fluorescent-labeled LP-SERT in the liver and spleen of mice even after 48 h of administration. This study demonstrates the efficacy of PS liposomes containing sertraline in experimental VL. Considering the urgent need for VL treatments, the repurposing approach of SERT could be a promising alternative. (AU)